Taste masking of bitter drug powder without loss of bioavailability by heat treatment of wax-coated microparticles.
Indeloxazine hydrochloride (IDX), a cerebral activator, has a bitter astringent taste. To prepare powders of IDX without this bitter taste, microparticles (median diameter, 130 microns) of IDX were coated with a mixture comprising hydrogenated oil and surfactants in a fluidized bed using the side-spray method. Drug release from the resulting coated particles was significantly delayed. Dissolution rate was remarkably enhanced, however, by heat-treating the coated particles at a temperature above the melting point of the surfactant in the coated layer. The results of differential scanning calorimetry measurements show that part of the surfactant in the coated layer exists separately. Further, surface changes in the coated layer before and after heat treatment showed that this enhancement of dissolution rate was due to rediffusion of the surfactant in the coated layer followed by melting of the surfactant. This effect allows the design of powders of IDX which release the drug quickly and with bioequivalence to the commercial IDX 20 mg tablets while sufficiently suppressing the bitter taste.
Sugao
H
H
Novel Pharma Laboratories Institute for Drug Development Research, Shizuoka, Japan. sugao@yamanouchi.co.jp
Yamazaki
S
S
Shiozawa
H
H
Yano
K
K
D000928:Antidepressive Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D018592:Cross-Over Studies; D004339:Drug Compounding; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D009025:Morpholines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011060:Poloxalene; D011208:Powders; D012995:Solubility; D013649:Taste
D000928:Antidepressive Agents; D009025:Morpholines; D011208:Powders; C020852:indeloxazine; D011060:Poloxalene